Ergosterol/7-dehydrocholesterol

FIGURE 1, Photo- and thermal isomerizations of vitamin D isomers. E = ergosterol/7-dehydrocholesterol P = previtamin D L = lumisterol T = tachysterol ... 

In the first category of compounds (active) are cholestanol, erganostanol, sitostanol, m-cholestane-3,4-diol, ergosterol, 7-dehydrocholesterol, 22-di-hydrocholesterol, 7-dihydroergosterol, ergostenol, a-sistosterol, and cinchol. This indicates that the systems of the organism attach little importance to the unsaturated or saturated conditions of bonds 5-6, 7-8, or 22-23, to the presence or absence of a hydroxyl group at position 4, or to the position of branches on the side chain. 

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

Actually, neither vitamin D2 nor D3 is present in foods. Rather, foods contain the precursor molecules 7-dehydrocholesterol and ergosterol. In the presence of sunlight, however, both precursors are converted under the skin to the active vitamins, hence the nickname for vitamin D, the "sunshine vitamin. 7... 

The active vitamins are produced by conversion of provitamins by ultraviolet light. Ergosterol, a yeast sterol, is converted to its active form, ergocalciferol (vitamin D2), and 7-dehydrocholesterol, which is found in many natural foods and is also synthesized in man, is converted to cholecalciferol (vitamin D3). Fish liver oils are virtually the only source of vitamin D3 in nature. The most active form of vitamin D3 is 1,25-dihydroxycholecalciferol and this is produced by the hydroxylation of cholecalciferol at position 25 in the liver and then at position 1 in the kidney. 

Blood levels of vitamin D are influenced both by dietary intake and the amount of daylight exposure to the skin. Indeed, exposure of the skin to ultraviolet light catalyzes the synthesis of vitamin D3 (cholecalciferol) from 7-dehydrocholesterol thus vitamin D is more like a hormone and not strictly a vitamin. Furthermore, the UV radiation catalyzes the synthesis of ergocalciferol from ergosterol. This latter compound is found in plants, especially yeast and fungi, but the conversion to ergocalciferol... 

Cholecalciferol is pure vitamin D3 derived from the ultraviolet conversion of 7-dehydrocholesterol to cholecalciferol. Ergocalciferol vitamin D2) is a sterol derived from yeast and fungal ergosterol. Calcitriol [Rocaltrol, 1,25-(0H)2D3] is the metabolically active vitamin D3 compound. Dihydrotachysterol is a synthetic compound that may act somewhat more quickly than either vitamin D2 or D3. 

Vitamin D is the collective term for a group of compounds formed by the action of ultraviolet irradiation on sterols. Cholecalciferol (vitamin D3) and calciferol (vitamin D2) are formed by irradiation of the provitamins 7-dehydrocholesterol and ergosterol, respectively. The conversion to vitamin D3 occurs in the skin. The liver is the principal storage site for vitamin D, and it is here that the vitamin is hydroxylated to form 25-hydroxyvitamin D. Additional hydroxylation to form 1,25-dihydroxyvita-min D occurs in the kidney in response to the need for calcium and phosphate. A discussion of the role of vitamin D in calcium homeostasis is provided in Chapter 66. 

However, it was not until 1924, when Steenbock and Hess showed that irradiation of certain foods generated protective activity against the disease, that vitamin D (calciferol) was recognized as a second lipid-soluble vitamin. Vitamin D is a family of compounds formed by the irradiation of A5/7-unsaturated sterols such as ergosterol and 7-dehydrocholesterol. The former yields ergocalciferol (vitamin D2) and the latter cholecalciferol (vitamin D3). 

The most important or at least the best-known members of the family of D vitamins are vitamin D2 (calciferol), which is indicated in abbreviated form in Structure 1 and can be produced by ultraviolet irradiation of ergosterol, and vitamin D3 [Structure 2], which may be produced by the irradiation of 7-dehydrocholesterol. 

In the biosynthesis of vitamin D substances, precursors include cholesterol (skin + ultraviolet radiation) in animals ergosterol (algae, yeast + ultraviolet radiation), Intermediates in the biosynthesis include preergocaldferol, tachysterol, and 7-dehydrocholesterol. Provitamins in very small quantities are generated in the leaves, seeds, and shoots of plants. In animals, the production site is the skin. Target tissues in animals are bone, intestine, kidney, and liver. Storage sites in animals are liver and skin. 

Vitamin D is represented by cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2), which are structurally similar secosteroids derived from the UV irradiation of provitamin D sterols. In vertebrates, vitamin D3 is produced in vivo by the action of sunlight on 7-dehydrocholesterol in the skin. Vitamin D2 is produced in plants, fungi, and yeasts by the irradiation of ergosterol. On irradiation, the provitamins are converted to previtamin D, which undergoes thermal transformation to vitamin D. 

Vitamin D-active substances are required in the diets of growing children and pregnant women, but normal adults receiving sufficient doses of sunshine can manufacture sufficient amounts of these compounds to meet their needs. Active vitamin D compounds can by synthesized in such individuals from 7-dehydro-cholesterol (see Table 6.2), an intermediate in cholesterol biosynthesis. Dietary sources also include cholecalciferol, which is produced from 7-dehydrocholesterol and ergosterol (Table 6.2). 7-Dehydrocholesterol and ergosterol are often referred to as provitamins. 

The precursors of vitamins D2 and D3 are ergosterol and 7-dehydrocholesterol, respectively. These precursors or provitamins can be converted into the respective D vitamins by irradiation with ultraviolet light. In addition to the two major provitamins, there are several other sterols that can acquire vitamin D activity when irradiated. The provitamins can be converted to vitamin D in the human skin by exposure to sunlight. Because very few foods are good sources of vitamin D, humans have a greater likelihood of vitamin D deficiency than of any other vitamin deficiency. Enrichment of some foods with vitamin D has significantly helped to eradicate rickets, which is a vitamin D deficiency disease. Margarine and milk are the foods commonly used as carrier for added vitamin D. 

A requirement for A -sterols seems to be satisfied in different species by different methods. Whereas starfish reduce the A -double bond of cholesterol before introducing the A -double bond/ in Paramecium aurelia cholesterol (A ) is converted into 7-dehydrocholesterol In Penicillium rubrum ergosterol... 

A-11 Ergosterol and pro-vitamin D, 7-dehydrocholesterol, in the skin have the same structure except ergosterol has one more double bond in the side chain between C22 and C23 and has one more methyl group at C24. Both the provitamin D and ergosterol are converted to active vitamin D by UV radiation. 

The anti-rachitic factors resulting from the ultraviolet irradiation of cholesterol (40) and ergosterol (41) namely vitamin Dj (42) cholecalciferol and Dj, ergocalciferol (43) respectively are important dietary materials the chemistry of which was only elucidated by the investigations of many chemists (ref.41). Vitamin Dj is most easily derived by semi-synthesis from cholesterol through formation firstly of 7-dehydrocholesterol by reaction with N-bromosuccinimide followed by dehydrobromination with collidine. Ultraviolet light irradiation affords previtamin Dj which is thermally isomerised to the endo compound shown and thence to the exo... 

Chemistry. There are two forms of vitamin D, and both are considered biologically equivalent. Irradiation of the major plant sterol, ergosterol, produces ergocalciferol, also known as vitamin Dg (Fig. 8.11).Because they are photochemical reactions and in contrast to enzyme-catalyzed biochemical reactions, the formation of cholecalciferol is not clean. Exposure of human skin to sunlight of295-300 nm converts 7-dehydrocholesterol to provitamin D,. The isomerization to cholecalciferol (vitamin Dg) is heat catalyzed. Continuous exposure to ultraviolet radiation from the sun results in the reversible formation of lumisterol... 

Vitamin D is a fat soluble vitamin derived from cholesterol. In the human epidermis (skin), sunlight spontaneously oxidizes cholesterol to 7-dehydrocholesterol (Fig. 10.10a). The 7-dehydrocholesterol leaks into the blood where it isomerizes to cholecalciferol (vitamin D3, Fig. 10.10b and c). Cholecalciferol is enzymatically hydroxylated at C25 in the liver (25-cholecalciferol) and then passes to the kidney where another enzyme is activated by parathyroid hormone to hydroxylate it at Cl, forming calcitriol (Fig. lO.lOd). The kidney hydroxylase is sensitive to feedback inhibition. As the amount of calcitriol increases, it binds to the hydroxylase and alters the specificity of the kidney enzyme. Additional 25-cholecal-ciferol is hydroxylated to 24,25-dihydroxycholecalciferol (inactive calcitriol) instead of 1,25 dihydroxycholecalciferol (calcitriol). Other vitamin D derivatives that can be converted to calcitriol are obtained enzymatically from cholesterol in other vertebrates. The most common of these are vitamin D3 (lamisterol) and D2 (ergosterol) from cold-water fish such as cod, where their presence keeps membranes fluid at low body temperatures 10-20°C. 

Vitamin D2 is mannfactured by UV-radia-tion of ergosterol and vitamin Dj is obtained from tuna fish liver oil and UV-radiation of 7-dehydrocholesterol. 

Since the first rigorous demonstration of the dealkylative conversion of ergosterol into 22-dehydrocholesterol in the German cockroach Blattela germanica, several reports have appeared on the conversion of phytosterols into cholesterol in a variety of insects. The biochemical mechanism of the conversion has been investigated in... 

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